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Adjunct Phentermine + Topiramate After Bariatric Surgery in 12-24 Year Olds

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ClinicalTrials.gov Identifier: NCT04095104
Recruitment Status : Not yet recruiting
First Posted : September 19, 2019
Last Update Posted : September 19, 2019
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado- Clinical and Translational Sciences Institute
University of Colorado- Nutrition Obesity Research Center
Information provided by (Responsible Party):
Jaime Moore, MD MPH, Children's Hospital Colorado

Brief Summary:
The goal of this pilot study is to establish the feasibility and initial efficacy of the combination of phentermine and topiramate for adolescents and young adults who require additional risk reduction after bariatric surgery. This study will use a randomized, placebo-controlled, double-blinded design to evaluate an adjunctive 12-week intervention of phentermine + topiramate + standard of care vs. placebos + standard of care 6 months after bariatric surgery, among 12 to 24 year olds who don't achieve expected weight loss or who remain severely obese (n=10 total).

Condition or disease Intervention/treatment Phase
Obesity, Morbid Bariatric Surgery Adolescent Young Adult Drug Therapy Drug: Phentermine Drug: Immediate Release Topiramate Drug: Placebo for Phentermine Drug: Placebo for Immediate Release Topiramate Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two-arm parallel assignment where the experimental arm will receive active drugs + standard of care and the control arm will receive placebo drugs + standard of care.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: At baseline, each participant will be randomized 1:1 to either 12 weeks of phentermine, topiramate and standard of care or 12 weeks of phentermine placebo, topiramate placebo, and standard of care. This randomization will be blinded to the participant, investigator, care providers, and outcomes assessor for the duration of the study.
Primary Purpose: Treatment
Official Title: Adjunctive Anti-Obesity Pharmacotherapy in Adolescents and Young Adults After Bariatric Surgery: A Randomized Controlled Pilot Study
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phentermine & Topiramate

Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration:

4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning

+

Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning

+

Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)

Drug: Phentermine
Phentermine tablet
Other Names:
  • Lomaira
  • Adipex-P
  • C045TQL4WP
  • 2-methyl-1-phenylpropan-2-amine

Drug: Immediate Release Topiramate
Topiramate tablet
Other Names:
  • Topamax
  • 0H73WJJ391
  • [(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydrodi[1,3]dioxolo[4,5-a:5',3'-d]pyran-3a-yl]methyl sulfamate

Placebo Comparator: Placebo Drugs

Placebo Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration: 4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning

+

Placebo Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning

+

Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)

Drug: Placebo for Phentermine
Compounded tablet to mimic phentermine 8mg tablet

Drug: Placebo for Immediate Release Topiramate
Compounded tablet to mimic immediate release topiramate 25mg tablet




Primary Outcome Measures :
  1. Enrollment Rate [ Time Frame: 8 months ]
    Number enrolled divided by number eligible

  2. Dropout Rate [ Time Frame: 8 months ]
    Number who do not complete the study divided by number enrolled

  3. Adherence to Study Drugs [ Time Frame: 12 weeks ]
    Percentage of missed doses (pill count); Presence/Absence of amphetamine in the urine

  4. Frequency of drug-related adverse events [ Time Frame: 8 months ]
    Count and description of adverse events possibly or definitely related to the study drugs. Elicited using a standardized checklist during 3 study phone calls and 3 in-person study visits, laboratory monitoring of serum bicarbonate, and comprehensive review of systems, vitals, physical exam, and mood/suicidality assessment using validated instruments at every study visit.


Secondary Outcome Measures :
  1. Percent weight change [ Time Frame: Baseline and 12 weeks ]
    (Baseline weight - Weight at 12 weeks)/Baseline weight x 100

  2. Percent BMI change [ Time Frame: Baseline and 12 weeks ]
    (Baseline BMI - BMI at 12 weeks)/Baseline BMI x 100

  3. Change in BMI percent of the 95th%ile [ Time Frame: Baseline and 12 weeks ]
    (Baseline BMI % of the 95th%ile - BMI % of the 95th%ile at 12 weeks)

  4. Change in heart rate [ Time Frame: Baseline and 12 weeks ]
    (Heart rate at baseline - Heart rate at 12 weeks)

  5. Change in systolic blood pressure [ Time Frame: Baseline and 12 weeks ]
    Systolic blood pressure at baseline - Systolic blood pressure at 12 weeks

  6. Change in diastolic blood pressure [ Time Frame: Baseline and 12 weeks ]
    Diastolic blood pressure at baseline - Diastolic blood pressure at 12 weeks

  7. Change in total cholesterol (mg/dL) [ Time Frame: Baseline and 12 weeks ]
    Total cholesterol at baseline - Total cholesterol at 12 weeks

  8. Change in triglycerides (mg/dL) [ Time Frame: Baseline and 12 weeks ]
    Triglycerides at baseline - Triglycerides at 12 weeks

  9. Change in LDL cholesterol (mg/dL) [ Time Frame: Baseline and 12 weeks ]
    LDL at baseline - LDL at 12 weeks

  10. Change in HDL cholesterol (mg/dL) [ Time Frame: Baseline and 12 weeks ]
    HDL at baseline - HDL at 12 weeks

  11. Change in alanine aminotransferase (ALT) (U/L) [ Time Frame: Baseline and 12 weeks ]
    ALT at baseline - ALT at 12 weeks

  12. Change in hemoglobin A1c (HbA1c) (%) [ Time Frame: Baseline and 12 weeks ]
    HbA1c at baseline - HbA1c at 12 weeks

  13. Change in % fat mass [ Time Frame: Baseline and 12 weeks ]
    % Fat mass at baseline - %Fat mass at 12 weeks measured by DEXA

  14. Change in resting metabolic rate (RMR) [ Time Frame: Baseline and 12 weeks ]
    RMR at baseline - RMR at 12 weeks measured by indirect calorimetry

  15. Change in Dietary Intake [ Time Frame: Baseline and 12 weeks ]
    The adolescent/young adult will complete a dietary record on 3 consecutive days (2 weekdays, 1 weekend day) based on standardized protocols for dietary assessment. Total caloric intake, macronutrient, and micronutrient breakdown will be assessed.

  16. Change in Hunger [ Time Frame: Baseline and 12 weeks ]
    The adolescent/young adult will report hunger before each meal and snack for 24 hours using a 100mm visual analogue scale (0= no hunger, 100 = most hunger)

  17. Change in Satiety [ Time Frame: Baseline and 12 weeks ]
    The adolescent/young adult will report satiety before each meal and snack for 24 hours using a 100mm visual analogue scale (0= no fullness, 100= most full)

  18. Change in Eating in the Absence of Hunger [ Time Frame: Baseline and 12 weeks ]

    Validated questionnaire: Eating in the Absence of Hunger-Parent (EAH-P) completed by the parent/guardian about their adolescent/young adult. This measure has 14 items.

    Each item is on a 5-point Likert scale ranging from 1= "never" to 5= "always". A higher score indicates more eating in the absence of hunger.

    Total and sub scales are calculated by taking the average of the items. Total score measures the overall construct "Eating in the Absence of Hunger" Subscales include: "External Cues" (4 items); "Response to negative affect" (6 items); "Fatigue/Boredom" (4 items).


  19. Change in Cognitive Restraint, Disinhibited Eating, and Predisposition to Hunger [ Time Frame: Baseline and 12 weeks ]

    The "Three-Factor Eating Questionnaire" will be completed by the adolescent/young adult. This is a 51-item measure that is divided into 2 parts, and assesses 3 eating behaviors: 1) Cognitive Dietary Restraint (20 items), 2) Disinhibited Eating (16 items), and 3) Predisposition to hunger (15 items). Higher scores in each domain indicate more of each of those behaviors.

    The minimum score for factors 1, 2, and 3 are: 0, 0, and 0. The maximum score for factors 1, 2, and 3 are: 20, 16, and 15 Part I includes items 1-36 rated as either True (1) or False (0) Part II includes items 37-51 and is rated on a 4-point Likert-like scale with one exception- item 50 is rated on a 6-point scale.

    Scores for each of the three eating behaviors are calculated by taking the average of the items, and are most commonly reported separately, not as a total score.


  20. Change in Weight Related Quality of Life- Adolescent [ Time Frame: Baseline and 12 weeks ]

    "Impact of Weight on Quality of Life-Kids" questionnaire will be completed by the adolescents age <=19.

    Total and each of the 4 sub scales (Physical Comfort-6 items, Body Esteem-9 items, Social Life-6 items, and Family Relations-6 items) range from a minimum score of 0 to a maximum of 100.

    Higher scores indicate higher quality of life.


  21. Change in Weight Related Quality of Life- Parent [ Time Frame: Baseline and 12 weeks ]

    "Impact of Weight on Quality of Life-Kids Parent Proxy" questionnaire will be completed by the parent of the adolescent/young adult.

    Total and each of the 4 sub scales (Physical Comfort-6 items, Body Esteem-9 items, Social Life-6 items, and Family Relations-6 items) range from a minimum score of 0 to a maximum of 100.

    Higher scores indicate higher quality of life.


  22. Change in Weight Related Quality of Life- Young adult [ Time Frame: Baseline and 12 weeks ]

    "Impact of Weight on Quality of Life-Lite" questionnaire will be completed by the young adult age >=20.

    Total and each of the 5 sub scales (Physical function-11 items, Self Esteem-7 items, Sexual Life-4 items, Public distress-5 items, and Work-4 items) range from a minimum score of 0 to a maximum of 100.

    Higher scores indicate higher quality of life.


  23. Change in General Health Related Quality of Life: PedsQL instrument [ Time Frame: Baseline and 12 weeks ]

    PedsQL instrument will be completed by the adolescent/young adult. There are 4 scales: Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items) and 3 Summary Scores: Total Scale Score (23 items), Physical Health Summary Score (8 items), and Psychosocial Health Summary Score (15 items).

    Items are rated on a 0-4 scale. Items are reverse scored and linearly transformed to a 0-100 scale, such that 0=100, 1=75, 2=50, 3=25, and 4=0.

    Higher scores indicated better health-related quality of life. Scale Scores are calculated as the sum of the items over the number of items answered.

    Psychosocial Health Summary Score is calculated as the sum of the items over the number of items answered in the Emotional, Social, and School Functioning Scales.

    Physical Health Summary Score is the same as the Physical Functioning Scale Score.


  24. Change in Depression [ Time Frame: Baseline and 12 weeks ]

    The adolescent/young adult will complete the 20-item Center for Epidemiologic Studies Depression Scale (CES-D).

    Each item is rated on a 0 to 3 scale (positive items are reverse scored). Minimum score is 0 and maximum is 60. Higher scores indicate more depressive symptoms. Total score is calculated by summing each of the 20 individual items scores.


  25. Participant Satisfaction: questionnaire [ Time Frame: At 12 weeks ]
    The participating family will be asked to complete a satisfaction questionnaire that will assess reasons for participation, experience during study visits, satisfaction with the effect of the study drug, ease of communication with study staff, and study burden.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Status post sleeve gastrectomy or roux-en-y gastric bypass
  • At 6 months after bariatric surgery, has not achieved >= 26% decrease in weight from preoperative weight (within 1 week of surgery) OR remains severely obese (>=120% of 95th%ile or BMI >=35kg/m2 for 12-17yo; BMI >=35kg/m2 for 18-24yo)

Exclusion Criteria:

  • Absolute contraindication to phentermine or topiramate (i.e. phentermine:

history of coronary artery disease, stroke, arrhythmia, congestive heart failure, uncontrolled hypertension), hypersensitivity to sympathomimetic amines, current or recent (within 14 days) use of monoamine oxidase inhibitors, glaucoma, or hyperthyroidism; topiramate: hypersensitivity to topiramate, history of nephrolithiasis)

  • Concomitant use of phenytoin, carbamazepine, or carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, or dichlorphenamide)
  • Use of anti-obesity medication within 6 months of screening
  • Initiation of a new medication associated with weight loss or gain within 30 days of screening
  • Type 2 diabetes mellitus
  • Hypothalamic obesity
  • Unmanaged (e.g. without medications and/or psychotherapy) clinically significant (determined by a mental health professional using diagnostic instruments and/or clinical interview) depression or anxiety
  • History of any suicidal behavior within 30 days of screening or any suicidal ideation with either some intent to act or with intent and a specific plan within 30 days of screening
  • History of schizophrenia
  • Severe hepatic impairment (ALT >10x upper limit of normal or known synthetic liver dysfunction)
  • Moderate or severe renal impairment (GFR <30mL/min/1.73m2)
  • Dosage change to hypertension, dyslipidemia, depression, or anxiety medication <4 weeks prior to study enrollment
  • Contraception started <7 days prior to study enrollment
  • Current pregnancy/plans to become pregnant within 16 weeks from study drug start date
  • Females without a long acting reversible contraceptive (LARC) who do not commit to using 2 forms of birth control

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04095104


Contacts
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Contact: Jaime M Moore, MD, MPH 303-724-8419 jaime.moore@cuanschutz.edu
Contact: Megan M Kelsey, MD, MS megan.kelsey@childrenscolorado.org

Locations
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United States, Colorado
Children's Hospital Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Jaime M Moore, MD, MPH    303-724-8419    jaime.moore@cuanschutz.edu   
Contact: Megan M Kelsey, MD, MS       megan.kelsey@childrenscolorado.org   
Principal Investigator: Jaime M Moore, MD, MPH         
Sub-Investigator: Megan M Kelsey, MD, MS         
Sub-Investigator: Thomas H Inge, MD, PhD         
Sub-Investigator: Richard E Boles, PhD         
Sub-Investigator: Marc-Andre Cornier, MD         
Sponsors and Collaborators
Jaime Moore, MD MPH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado- Clinical and Translational Sciences Institute
University of Colorado- Nutrition Obesity Research Center
Investigators
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Principal Investigator: Jaime M Moore, MD, MPH University of Colorado School of Medicine

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Responsible Party: Jaime Moore, MD MPH, Assistant Professor of Pediatrics, Section of Nutrition, Children's Hospital Colorado
ClinicalTrials.gov Identifier: NCT04095104     History of Changes
Other Study ID Numbers: 18-2793
5P30DK048520-24 ( U.S. NIH Grant/Contract )
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jaime Moore, MD MPH, Children's Hospital Colorado:
Pilot
Feasibility
Initial Efficacy
Randomized Controlled Trial
Additional relevant MeSH terms:
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Obesity
Obesity, Morbid
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Topiramate
Phentermine
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs
Central Nervous System Stimulants
Appetite Depressants
Anti-Obesity Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action